The proposed program will continue our studies on the mechanisms involved in the growth of picornaviruses. The major focus will be on poliovirus RNA replication. Purification of both the host and viral proteins that make up the replicase system is planned. The mechanism of initiation of viral RNA replication and the possible involvement of a protein primer will be examined. Three other areas of proposed investigation are: the mechanism of virus-induced inhibition of host cell protein synthesis; studies of the role of protein NCVPX in the viral life cycle; and derivation of a cloned DNA replica of the poliovirus genome in an E. coli plasmid and studies of its infectivity and structure.